When to Start Paxlovid for COVID-19 Treatment
Paxlovid (nirmatrelvir/ritonavir) should be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset in patients with mild to moderate COVID-19 who are at high risk for progression to severe disease. 1, 2, 3
Patient Selection Criteria
High-Risk Patients (Strong Recommendation)
- Advanced age (especially ≥65 years)
- Uncontrolled chronic medical conditions
- Immunocompromised status
- Unvaccinated status
- Pregnancy (can be considered a high-risk condition) 2
Moderate-Risk Patients (Conditional Recommendation)
- May be considered for Paxlovid treatment due to reduction in hospitalization risk 2
Low-Risk Patients
- Not recommended as benefits are considered trivial 2
Timing and Administration
- Treatment must be initiated within 5 days of symptom onset 1, 2, 3
- Standard dosing: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days 2, 3
- Tablets should be swallowed whole (not chewed, broken, or crushed) 3
- Can be taken with or without food 3
Dosage Adjustments
Renal Impairment 2, 3
- Moderate impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days
- Severe impairment (eGFR <30 mL/min):
- Day 1: 300 mg nirmatrelvir with 100 mg ritonavir once
- Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily
- For hemodialysis patients: Administer after hemodialysis
Hepatic Impairment 2, 3
- Mild to moderate impairment: No dosage adjustment needed
- Severe impairment (Child-Pugh Class C): Not recommended
Drug Interaction Assessment
- Prior to prescribing Paxlovid, review all medications to assess potential drug-drug interactions 2, 3
- Ritonavir is a strong CYP3A inhibitor that can cause significant drug-drug interactions 3
- Use the Liverpool COVID-19 Drug Interaction Tool to check potential interactions 2
- Determine if concomitant medications require:
- Dose adjustment
- Temporary interruption
- Additional monitoring 3
Contraindications
- History of clinically significant hypersensitivity reactions to nirmatrelvir or ritonavir 3
- Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations are associated with serious reactions 3
- Co-administration with potent CYP3A inducers 3
Clinical Benefits
- Paxlovid reduces hospitalization and death in high-risk patients 2, 4
- A large electronic health record study of 703,647 patients showed:
- 39% reduction in risk of hospitalization (absolute risk reduction of 0.9 percentage points)
- 61% reduction in risk of death (absolute risk reduction of 0.2 percentage points) 4
- Benefits observed across all age groups but particularly significant in patients aged 65+ years 4
- Effective in both vaccinated and unvaccinated patients 4, 5
Alternative Therapies When Paxlovid is Contraindicated
- Remdesivir: Consider when Paxlovid is contraindicated due to drug interactions (requires intravenous administration over 3 days) 2
- Molnupiravir: Less effective than Paxlovid but can be considered when other options are unavailable (must also be started within 5 days of symptom onset) 2
Common Pitfalls and Caveats
- Failure to screen for drug interactions - Review all medications before prescribing 3
- Delayed initiation - Efficacy decreases with delayed treatment; start within 5 days of symptom onset 1, 2, 3
- Improper dosing in renal impairment - Adjust dose based on renal function 2, 3
- COVID-19 rebound - Recurrence of symptoms or positive test results 2-8 days after recovery has been documented but is rare 6
- Inequitable access - Lower treatment rates have been observed among Black and Hispanic/Latino patients and within socially vulnerable communities 4
Paxlovid is a valuable tool in reducing COVID-19 morbidity and mortality when initiated promptly in appropriate high-risk patients, with careful attention to potential drug interactions and proper dosing based on renal function.